消化科开题报告

Tim-3/galectin-9pathway:regulationofTh1immunitythroughpromotionofCD11bLy-6Gmyeloidcells研究背景分泌IL-2、IFN-γ、TNF介导细胞免疫

ThTh1Th2Th17Treg分泌IL-4、IL-5、IL-10、IL-13介导体液免疫反应分泌IL-17,IL-21,andIL-22分泌IL-10、TGFβ免疫抑制Th1自免病胞内菌肿瘤Tim3，即T细胞免疫球蛋白及粘附素结构域蛋白3表达在Th1细胞表面，是其标志分子与其配体Galectin9结合致Th1细胞减少，调节免疫反应Galectin9Th1细胞凋亡Tim3Th1Galectin9Tim3材料及方法试验动物:Tim-3transgenicmiceGalectin-9transgenicmiceTim-3−/−miceRag1−/−C57BL/6mice:无T和B细胞

Galectin-9transgenicandTim-3−/−mice试验方法:FlowCytometryTcellproliferationtestELISAReal-timePCR

模型建立:肿瘤模型：Miceinjectedwith5×105-1×106

EL4cells(thymomacellsfromC57BL/6)withintherightflank.1×1054T1cells(mammaryadenocarcinomafromBalb/c)wereinjectedintomammarytissue

EAE模型：实验性自身免疫性脑脊髓炎injectedsubcutaneouslywith100µgofMOG35–55peptide(MEVGWYRSPFSRVVHLYRNGK)emulsifiedinCFA(Difco)supplementedwith4µgml−1Mycobacteriumtuberculosisandinjectedtwiceintravenouslywith100ngofpertussistoxin(ListBiologicalLaboratories).NotesCD44highCD62Llow：effector/memoryTcellCD44lowCD62Lhigh：naivecellCD11b+：monocyte/macrophageandgranulocyteF4/80:monocyte/macrophageandeosinophilGr-1:inflammatorymonocyteandgranulocyteLy-6GandLy-6C:CD11b+cellTNP-OVA: 三硝基苯酚-卵清蛋白，为抗原，具有刺激免疫反应作用Tim3转基因小鼠实验WildTim3TgthymusCD4+SPCD8+SPSpleenCD4+CD8+EffectorMemoryTcellCD11b+APCBcellCD3分泌反应增殖反应增殖反应分泌反应F4/80Gr-1与CD4+细胞小鼠肿瘤接种实验WildTim3TgTim3-/-WildEL-44T1controlTim3抗体TumorgrowthCD11b+Gr-1+cellBecauseGr-1antigenconsistsoftheepitopesfrombothLy-6GandLy-6C,sotheyexaminedthesetwomolecularswithspecificantibodiesandtheyfoundTim3TgmicehadmoreCD11b+cellsthatwereLy-6G+F4/80lowLy-6ClowWildTim3TgTim3-/-WildEL-44T1controlTim3抗体TumorgrowthCD11b+Gr-1+cellWildTim3TgEAECNSCD11b+Ly-6G+F4/80low发病率EAE模型试验DoestheTim3expressedonTcellstriggertheexpansionofCD11b+Ly-6+F4/80lowcellsinvivo?Ly-6G+F4/80lowCD11b+cellRag敲除小鼠CD4+Tim3+CD4+Tim3-4-6周后取脾细胞cellularityBACKBACKBACKBACKGalectin9转基因小鼠实验WildGal9Tg淋巴结脾脏CD11b+抗CD3Tcell增殖反应分泌反应APCB细胞Effector/MemoryLy-6G+F4/80low

TNP-OVA刺激TNP-OVA刺激PICPICPICPICPICBACKBACKBACKBACKBACKHowcouldbothTim3anditsligandgalectin9independentlyresultintheexpansionofCD11b+Ly-6+F4/80lowcells

CD11b+Ly-6+CD11b+Ly-6-ControlIFN-g检测Galectin9WhetheradirectinteractionofTim3withgalectin9isresponsiblefortheexpansionofCD11b+Ly-6+F4/80lowcells

Wild淋巴结脾脏Tcell增殖反应分泌反应Effector/MemoryLy-6G+F4/80low

TNP-OVA刺激TNP-OVA刺激Gal9TgGal9TgTim3-/-

CD11b+PICPICPICPICBACKBACKBACKBACKConclusion

Tim-3/galectin-9pathwayregulatesTh1immuneresponsesthroug